CA2068606C

CA2068606C - Dentifrice compositions

Info

Publication number: CA2068606C
Application number: CA002068606A
Authority: CA
Inventors: Philip Christopher Waterfield
Original assignee: Unilever PLC
Current assignee: Unilever PLC
Priority date: 1991-05-17
Filing date: 1992-05-13
Publication date: 1996-10-15
Anticipated expiration: 2012-05-13
Also published as: CA2068606A1; EP0514966A2; ES2075594T3; AU648892B2; ATE124862T1; EP0514966A3; JPH0713009B2; EP0514966B1; AU1630992A; JPH05148125A; US5258173A; BR9201852A; DE69203391T2; DE69203391D1; ZA923553B; GB9110721D0

Abstract

The present invention relates to a dentifrice composition comprising a stannous compound that releases stannous ions in the composition such as stannous fluoride or stannous pyrophosphate. These stannous ions can be converted in the composition into the inactive stannic ions, and to prevent such conversion according to the present invention an antioxidant is incorporated into the composition, such as butylated hydroxyanisole, butylated hydroxytoluene and ethyl vanillin.

Description

~ /- 2068606 "DENTIFRICE CQMPOSITIONS" - ~
BACRGROUND OF TEIE INV~NTIQN ~ ~ =

Pield o~ the Invention The present invention relates to dentifrice compositions containing stannous 10 Related ~r~
There have been many proposals in the prior art to in~.:ULyuLate ~ UUI ~ ds into oral health Câre products for the purpose of achieving particular cl;n;c~l benefits such as caries prevention, plaque control or the 15 reduction of gingivitis. These stannous ~ ,ullds are compounds which, upon association with water, are capable of yielding ~Lallllvus ions, as it is actually the stannous ion which is active against oral bacteria.
20 ~owever, the incuL~oLal.ion of stannous c _ ~- into dentifrice compositions presents problems in that the stannous ions tend to react with other ~ ts of the dentifrice composition to form insoluble stannous , which reduces the effective amount of stannous 25 ions in the composition and thus renders the stannous - olln~ less efficacious. In addition, the active stannous ion is particularly prone to oxidation, e.g. by air or an oxidizing agent, the stannous ion being converted thereby into the inactive stannic form.
In GB-A-804,486 it is proposed to uvt:ruu~ the problem that stannous ions react with other components of a dentifrice composition by using a slightly soluble stannous compound e. g. stannous pyrophosphate, thus 35 maintaining a "reservoir" of stannous tin in the form of an undissociated stannous compound which replenishes stannous ions that have reacted with other components of the dentifrice composition. ~_ 2 J 7025 ~R) We have found, however, that the inclusion of such slightly soluble stannous ~ uullds, e.g. stannous pyrorhc ~rh~te, still gives rise to the formation of inactive stannic compounds.
According to the present invention it has now been found that the conversion of stannous ions in a dentifrice composition into inactive stannic ions can be signif icantly reduced or prevented by the inclusion in the 10 dentifrice composition of an antioxidant which is a radical inhibitor. Since dentifrice compositions do not normally contain an oxidizing agent and are usually packed in a closed container, it was quite ~-nF-Yrect~cl that the use of an antioxidant of the radical inhibitortype did 15 significantly reduce and prevent the conversion of stannous ions into stannic ions in such a dentifrice composition .
SU~5hAR5r OF ~HE INVBNTIoN
20 Consequently, in its broadest aspect, the present invention embraces a dentifrice composition which comprises an effective amount of a stannous, _ a capable of yielding stannous ions upon association with water, and an effective amount of an antioxidant which is 25 a radical inhibitor capable of reducing or preventing the conversion of the stannous ions in the dentifrice composition into stannic ions.
DE~JT Rn DESCRIPTION
30 The stannous ~ '~ which are suitable for inclusion in dentifrice compositions are known per se. Typical examples of suitable stannous, _llds are stannous compounds with inorganic or organic counter-ions. It can be a highly soluble stannous salt, or it can be a sparingly soluble 35 stannous salt. Highly soluble stannous salts are e.g.
stannous fluoride, stannous chloride, stannous chloride fluoride, stannous acetate, sodium stannous fluoride, ~ 2068606 3 J ~25 tR) potassium stannous fluoride, stannous hexafluorozirconate, stannous sulphate, stannous tartrate, stannous gluconate, etc. Of these highly soluble stannous salts, stannous fluoride is the preferred stannous salt.

Sparingly soluble stannous salts are e . g . stannous pyrophosphate, stannous met~rhnsrh~te, stannous oxalate, stannous phosphate, etc. Stannous pyrophosphate is a preferred sparingly soluble stannous salt. Mixtures of various highly soluble 6tannous salts may also be used, as well as mixtures of various sparingly soluble stannous salts and mixtures of highly and sparingly soluble stannous salts. A preferred mixture is the mixture of stannous fluoride and stannous pyrophnsrh~te.
In general, the stannous salt is used in such an amount in the oral composition that there is an effective amount of active dissolved stannous ions available in the composition to achieve an anti-caries, antigingivitis or anti-plaque efficacy. For the highly soluble stannous salts, this amount will generally range from 0.01-10%, preferably from 0.02-5%, and particularly preferably from 0.1-3% by weight of the oral composition. As regards the sparingly soluble stannous salts, these ranges are 0.05-10@, preferably 0.1-5%, and particularly preferably 0.1-3% by weight of the oral composition.
Antioxidants which are radical inhibitors are known per ~e. Both synthetically made or naturally occurring ant;nY;-lAnts are suitable in the present invention.
Typical examples of suitable antioxidants in the present invention are propyl gallate, butylated hydroxyanisole (BIIA), butylated llydL~,xyLoluene (BHT), ethyl vanillin, rosemary oil, lecithin, vitamin E, rutin, morin, fisetin and other bioflavonoids. Mixtures of various ant;oY;rl~ntc can also be used.

4 J 7025 (R) The antioxidant is used in an effective amount to significantly reduce or prevent the conversion of stannous ions into stannic ions. In general, low amounts of the antioxidants are already sufficient. Thus, the amount may range from 0.001-2%, usually from 0.015-1.5%, and preferably from 0.02-1% by weight of the dentifrice composition. Naturally, within the above framework the type of antioxidant and the level thereof will also be governed by ecological and safety approval factors.
Preferred antioxidants are BHA, BHT, and ethyl vanillin.
The oral composition of the present invention may contain an orally acceptable medium which contains usual additional ingredients in conventional amounts, depending upon the final form of the composition, i.e. a dentifrice, a mouthwash, a gel and the like. Thus, as a dentifrice it will usually comprise an abrasive cleaning agent in an amount of from 3-75 ~ by weight. Suitable abrasive cleaning agents are milled or unmilled particulate aluminas; silica xerogels, hydrogels and aerogels and precipitated particulate silicas; calcium pyrophosphate;
insoluble sodium metArh-cphAte; calcium carbonate;
~licA~ m orthophosphate; particulate llydLvxyc~patite and so on.
Furthermore, the dentifrice may contain a liquid phase comprising water and a l - ~nt in various relative amounts, in an amount of 10-99% by weight. Typical humectants are glycerol, sorbitol, polyethylene glycol, polypropylene glycol, propylene glycol, hydrogenated partially hydrolyzed polysaccharides and so on.
Binders or thickening agents such as sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, xanthan gums, Irish moss, gum tragacanth, f inely divided silicas and hectorites may also be included 2~686~
.
J 7025 ~R
in the dentifrice in an amount of 0.5-10% by weight.
Another conventional ingredient in a dentifrice is an organic surfactant such as soap, an 2nionic, nonionic, 5 cationic, ampholytic and/or a zwitterionic synthetic surfactant in an amount of 0 . 2-5% by weight.
~hen the composition is in the form of a mouthwash, it will usually contain an alcohol, a solubilizer and no 10 abrasive cleaning agent and when in the form of a gel, it will usually contain a thickening agent.
Various other optional ingredients may be i n~ in the compositions of the invention, such as flavouring agents, sw~ tDnin~ agents such as sodium saccharinate, whitening 15 agents such as titanium dioxide or zinc oxide, preservative6, vitamins such as vitamin C and E, other anti-plaque agents such as zinc salts, e.g. zinc citrate, copper salts, sanguinarine, allantoin, p-;~m;n-h-~n70ic acid derivatives, hexetidine, chlorhPs~i-9in.o, 3-(4-propylheptyl~
20 -4-(2 -llydLo~Ly~LIlyl) - morpholine, anti-bacterial agents such as Triclosan (2',4,4'-trichloro-2-hydroxy-diphenyl ether), anti~Al~lllus agents such as di- and/or tetra-alkali metal pyrophosphates, pH-adjusting agents, colouring agents, anti-caries agents such as casein, 25 casein digests, urea, calcium glycerorh-~srhAtes, sodium trimetArh~srhAte, sodium fluoride and -';um fluororhcfirhAte, anti-staining ullds such as silicone polymers, anti-inflammatory agents such as substituted 30 salicy1An;li~l~c, plant extracts, desensitizing agents for sensitive teeth such as potassium nitrate and potassium citrate, polymers such as polyvinyl methyl ether-maleic anhydride co-polymers and so on.
35 The present invention will now be further illustrated by the following Examples.

2068~

6 J 7025 (R) Five aqueous solutions of stannous fluoride, sodium lauryl sulphate and propyl gallate were prepared. The levels are 5 listed below:
SQlution ~Ei~ ~ ProPvl Gallate 0 . 5% 1. 5% 0% (Control) 2 0. 5% 1 . 5% 0 . 25%
3 0.5% 1.5% 0.5%
4 0 . 5% 1 . 5% 0 . 75%
0 . 5% 1. 5% 1. 00%
* All quantities are % w/v.

The solutions were made up in distilled water that had been purged with dry nitrogen gas f or 1 hour prior to use .
The SLS was added to solubilize the propyl gallate.
The solutions were left at 20C for 5 days. After this period, the solutions contained varying amounts of a white precipitate. Small aliquots of the whole solution were taken and analyzed, using Mr c~h~ r Spectroscopy. After 10 25 days, solutions 1 and 5 were analyzed by M~lc~::h~llr~r Spectroscopy again.
In addition to Mo$:~:h~tl~r Spectroscopy, the solutions were analyzed after 5 days for soluble stannous content by 30 polalu~L~l.y. However, unlike the samples taken for Mr c~:hall~r analysis, the samples for polarographic analysis were centrifuged first (3000 rpm, 30 minutes) to remove the f~occulent white precipitate.

~,. 2~ o~
r 7 J 7025 (R) ~Ol i-~Qqral~hic AnalYsis:
Solution Soluble Stannous ~evels/Pl~m ~ossbauer Analvsis:
10 5 ~AYS
Sn ( II ) Sn ( IV) Area o~ Sn ( IV) ' Solution ;L~ O . S .
3.15 1.88 -0.32 35 2 3 . 16 l . 79 -0 . 52 6 15 3 3 . 16 1. 80 -0. 57 4 4 3.19 1.77 -0.53 4 5 3 . 14 1 . 98 -0 . 58 5 20 1 3.11 1.98 -0.3~ 54 5 3.14 1.80 -0.57 6 -, 2a~8~06 .

8 J 7025 (R) * All figures given in mmsec-1 * Mossbauer errors +/- 0. 05 mmsec-1 * I.S. = Isomer Shift; Q.S. = Quadrupole Split.

It i5 clear from the polarographic analysis that increasing levels of propyl gallate inhibited the 10s8 of soluble stannous from solution. The polarograph, however, 10 only tests the stannous ~ I_s in solution. The M~cbAll~r spectra showed that with no propyl gallate present (solution 1), at least 34 of the total tin was Sn(IV) after 5 days and 549~ Sn(IV) at 10 days. Even with only 0.2596 of propyl gallate, after 5 days, there was only 15 approximately 6% of Sn(IV) and this level of Sn(IV) contamination was present in the starting materials anyway .
These data showed that the propyl gallate was inhibiting 20 the oxidation of Sn(Il) to Sn(IV).

9 2~68606 A series of 6 toothpastes have been formulated, containing different antioxldants. The formulations are listed below. The pastes ~rere stored at 50C for 1.7 months and analyzed, using Mossbauer Spectroscopy.

Paste 1 2 3 4 5 6 Silica xerogel 14 . 67 14 . 67 14 . 67 14 . 67 14 . 67 14 . 67 Silica aerogel g.43 9.43 9.43 9.43 9.43 9.43 Sorbitol (70%) 46.98 46.98 46.98 46.98 46.98 46.98 15Polyethylene glycol (MW 1500~ 5. 24 5 . 24 5 . 24 5 . 24 5 . 24 5 . 24 Xanthan gum 0 . 63 0 . 63 0 . 63 0 . 63 0 . 63 0 . 63 Saccharin 0.24 0.24 0.24 0.24 0.24 0.24 Sodium fluoride 0.34 0.34 0.34 0.34 0.34 0.34 20Benzoic acid 0.1965 0.1965 0.1965 0.1965 0.1965 0.1965 Titanium dioxide 1. 04 1. 04 1. 04 1. 04 1. 04 1. 04 Sodium lauryl - sulphate 1.5 1.5 1.5 1.5 1.5 1.5 25Stannous pyrorhosrh~te 1. 0 1. 0 1. 0 1. O 1. 0 1. O
Zinc citrate 0 . 5 0 . 5 0 . 5 0 . 5 0 . 5 0 . 5 Flavour 1.0 1.0 1.0 1.0 1.0 1.0 Special 30progallin 0.05 - - - - -Propyl gallate - 0 . 05 - - - -BIIA -- -- o . 07 Rosemary oil extract - - - 1. 0 0 35Ethyl vanillin - - - - 1. 00 BIIT -- -- -- - -- o . 03 Water 17 . 24 17 . 24 17 . 23 17 .14 17 .14 17 . 24 Total 100.00 100.00 lO0.00 100.00 lO0,00 100.00 J 7025 (R) Results ~
~nti~ nt SnfII) ~L Area of SnrIV) in Pastç I . S . O . S . I . S . Peak 96 ~r 5 Progallin 2 . 9S 2 .13 -0.15 5 (0.05%) 3.14 1.75 Propyl 2 . 93 2 .11 -0 .18 6 Gallate 3 .17 1. 81 (0 . 05%) 10 Butylated 2.94 2.10 -0.24 3 Hydroxyanisole 3 .14 1. 77 ( 0 07% ) Rosemary Oil 2.95 2.09 -0.21 4 Extract 3 .14 1. 77 15 Ethyl Vanillin 2.94 2.09 -0.19 6 (1~) 3.15 1.79 Butylated 2 . 94 2 .10 -0 . 22 4 HYdL ~ y Toluene 3 .15 1. 78 (0 . 03%) _ . .
.. . . . . . - . .... . _ .. . . ..
... .. .. ~ . , .

~ 2068606 11 J 7025 (R) Again, these data showed that the antioxidants inhibited the oxidation of Sn(Il) to Sn(IV).

A series of nine thoothpastes having the following formulations were stored for nine months at 37C, and the amount of Sn (IV) was determined using Mnccha~ r 10 spectroscopy. The amount of soluble Sn (II) was determined by polarographic analysis. Figures I and II show the results .
These results show, that the inclusion of antioxidants 15 have a beneficial effect on the stability of Sn (II), even in the presence of an additional 0.5~6 citrate, of which it is known that it can exert a soll~h;l;~;ng effect on Gtannous ions in certain formulations.

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Claims

1. A dentifrice composition comprising from 10 - 99 % by weight of a liquid phase comprising water and a humectant, from 0 - 75 % by weight of an abrasive cleaning agent, from 0.01 - 10 % by weight of a stannous compound, capable of yielding stannous ions upon association with water, and from 0.001 - 2 % by weight of an antioxidant which is a radical inhibitor capable of reducing or preventing the conversion of the stannous ions in the dentifrice composition into stannic ions selected from the group consisting of propyl gallate butylated hydroxyanisole, butylated hydroxytoluene, ethyl vanillin, rosemary oil, lecithin, vitamin E, rutin, morin fisetin and mixtures thereof.

2. The composition of claim 1, wherein the antioxidant is butylated hydroxyanisole, butylated hydroxytoluene or ethyl vanillin.

3. The composition of claim 1, wherein the stannous compound is stannous fluoride or stannous pyrophosphate.
.